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Development of a novel, automated, robotic system for rapid, high-throughput, parallel, solid-phase peptide synthesis
Krisztina Kiss1, Soma Ránky2, Zsuzsanna Gyulai2
1Tavanta Therapeutics Hungary Zrt., H-1138 Budapest, Hungary; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), H-1111 Budapest, Hungary.
SLAS Technology
|January 17, 2023
Summary
A new Tecan add-on peptide synthesizer (TaPSy) offers efficient, automated, and parallel peptide synthesis. This cost-effective system supports green chemistry principles and achieves high purity, advancing pharmaceutical research.
Area of Science:
- Medicinal Chemistry
- Organic Chemistry
- Chemical Engineering
Background:
- Peptide-based therapeutics are a significant area of pharmaceutical research and development.
- Existing solid-phase peptide synthesizers often lack efficiency, automation, scalability, cost-effectiveness, or adherence to green chemistry principles.
- There is a need for advanced peptide synthesis platforms to accelerate drug discovery and academic research.
Purpose of the Study:
- To introduce and evaluate a novel Tecan add-on peptide synthesizer (TaPSy).
- To demonstrate TaPSy's capabilities in terms of efficiency, automation, parallel synthesis, cost-effectiveness, and green chemistry compliance.
- To optimize synthesis parameters and assess the purity and yield of peptides produced by TaPSy.
Main Methods:
- Development of the Tecan add-on peptide synthesizer (TaPSy).
- Optimization of coupling reagents, reaction time, and reagent equivalents for model peptide synthesis.
- Evaluation of solvent flexibility, including the use of dimethylformamide (DMF) and the green solvent γ-valerolactone (GVL).
- Analysis of peptide purity, crude yield, and overall synthesis cost.
Main Results:
- TaPSy demonstrates operational flexibility with short coupling times (15-30 min) and handles manual synthesis methods.
- The system is economical, using minimal solvent (34.5 mL/cycle) at a 0.49 mmol scale per reactor.
- TaPSy enables parallel synthesis of up to 12 peptides and operates under ambient conditions (atmospheric pressure, room temperature, high humidity).
- Peptide synthesis using the green solvent GVL achieved high purity (>70%), comparable to DMF.
- Optimization studies identified effective synthesis conditions, balancing purity, yield, and cost.
Conclusions:
- TaPSy is a versatile, cost-effective, and robust peptide synthesizer suitable for both research and potential scale-up.
- The system supports green chemistry by enabling the use of renewable solvents like GVL without compromising peptide quality.
- TaPSy has the potential to accelerate peptide-based drug development and facilitate academic research in peptide science.
